Ivan Stankovic

Relationship of visually assessed apical rocking and septal flash to response and long-term survival following cardiac resynchronization therapy (PREDICT-CRT)

AIMS Apical rocking (ApRock) and septal flash (SF) are often observed phenomena in asynchronously contracting ventricles. We investigated the relationship of visually assessed ApRock and SF, reverse remodelling, and long-term survival in cardiac resynchronization therapy (CRT) candidates. METHODS AND RESULTS A total of 1060 patients eligible for CRT underwent echocardiographic examinations before and 12 ± 6 months after device implantation. Three blinded physicians were asked to visually assess the presence of ApRock and SF before device implantation and also their correction by CRT 12 ± 6 months post-implantation. Patients with a left ventricular (LV) end-systolic volume decrease of ≥15% during the first year of follow-up were regarded as responders. Patients were followed for a median period of 46 months (interquartile range: 27-65 months) for the occurrence of death of any cause. If corrected by CRT, visually assessed ApRock and SF were associated with reverse remodelling with a sensitivity of 84 and 79%, specificity of 79 and 74%, and accuracy of 82 and 77%, respectively. ApRock (hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.30-0.53, P < 0.0001) and SF (HR 0.45 [CI 0.34-0.61], P < 0.001) were independently associated with lower all-cause mortality after CRT and had an incremental value over clinical variables and QRS width for identifying CRT responders. Both the absence of ApRock/SF and unsuccessful correction of ApRock/SF despite CRT were associated with a high risk for non-response and an unfavourable long-term survival. CONCLUSION A specific LV mechanical dyssynchrony pattern, characterized by ApRock and SF, is associated with a more favourable long-term survival after CRT. Both parameters are also indicators of an effective therapy.

Dynamic relationship of left-ventricular dyssynchrony and contractile reserve in patients undergoing cardiac resynchronization therapy

AIMS Contradicting reports have been published regarding the relation between a dobutamine-induced increase in either cardiac dyssynchrony or left-ventricular ejection fraction (LVEF) and the response to cardiac resynchronization therapy (CRT). Using apical rocking (ApRock) as surrogate dyssynchrony parameter, we investigated the dobutamine stress echocardiography (DSE)-induced changes in left-ventricular (LV) dyssynchrony and LVEF and their potential pathophysiological interdependence. METHODS AND RESULTS Fifty-eight guideline-selected CRT candidates were prospectively enrolled for low-dose DSE. Dyssynchrony was quantified by the amplitude of ApRock. An LVEF increase during stress of >5% was regarded significant. Scar burden was assessed by magnetic resonance imaging. Mean follow-up after CRT implantation was 41 ± 13 months for the occurrence of cardiac death. ApRock during DSE predicted CRT response (AUC 0.88, 95% CI 0.77-0.99, P < 0.001) and correlated inversely with changes in EF (r = -0.6, P < 0.001). Left-ventricular ejection fraction changes during DSE were not associated with CRT response (P = 0.082). Linear regression analysis revealed an inverse association of LVEF changes during DSE with both, total scar burden (B = -2.67, 95CI -3.77 to -1.56, P < 0.001) and the DSE-induced change in ApRock amplitude (B = -1.23, 95% CI -1.53 to -0.94, P < 0.001). Kaplan-Meier analysis revealed that DSE-induced increase in ApRock, but not LVEF, was associated with improved long-term survival. CONCLUSION During low-dose DSE in CRT candidates with baseline dyssynchrony, myocardial contractile reserve predominantly results in more dyssynchrony, but less in an increase in LVEF. Dyssynchrony at baseline and its dobutamine-induced changes are predictive of both response and long-term survival following CRT.

Primary PCI for acute myocardial infarction in a patient with idiopathic thrombocytopenic purpura. A case report and review of the literature.

Background and Purpose:The occurrence of acute myocardial infarction (AMI) in patients with idiopathic thrombocytopenic purpura (ITP) is rare, especially when the platelet count is low. Since only few case reports have been published, there are no recommendations for the management of thrombocytopenic patients with AMI. The aim of the present study is to discuss different aspects of this challenging issue and to review limited data available in the literature.Case Study:An 80-year-old patient with ITP (platelet count 5 . 109/l) is presented who developed an AMI (ST segment elevation myocardial infarction) and was successfully treated by primary percutaneous coronary intervention (PCI).Conclusion:Considering the high bleeding risk in patients with ITP and AMI, careful balance between usual anticoagulation and antiplatelet therapy on the one hand, and efforts to raise platelet count on the other hand are needed.ZusammenfassungHintergrund und Fragestellung:Akute Myokardinfarkte (AMI) bei Patienten mit idiopathischer thrombozytopenischer Purpura (ITP, Morbus Werlhof) sind seltene Ereignisse. Da in der Literatur nur einige wenige Fälle beschrieben sind, existieren auch keine Therapieempfehlungen für diese Konstellation. In der vorliegenden Studie sollen unterschiedliche Aspekte dieser herausfordernden Situation diskutiert und die verfügbaren Daten aus der Literatur zusammenfassend beschrieben werden.Fallbericht:Geschildert wird der Fall eines 80-jährigen Patienten mit ITP (Thrombozytenzahl 5 . 109/l), der einen AMI (ST-Strecken-Hebungsinfarkt) erlitten hatte und mit primärer perkutaner Koronarintervention (PCI) erfolgreich behandelt wurde.Schlussfolgerung:Das hohe Blutungsrisiko bei Patienten mit ITP und AMI erfordert eine sorgfältige Balance zwischen Antikoagulation bzw. Plättchenhemmung einerseits und Anhebung der Thrombozytenzahl andererseits.

Primary PCI for Acute Myocardial Infarction in a Patient with Idiopathic Thrombocytopenic Purpura

Background and Purpose:The occurrence of acute myocardial infarction (AMI) in patients with idiopathic thrombocytopenic purpura (ITP) is rare, especially when the platelet count is low. Since only few case reports have been published, there are no recommendations for the management of thrombocytopenic patients with AMI. The aim of the present study is to discuss different aspects of this challenging issue and to review limited data available in the literature.Case Study:An 80-year-old patient with ITP (platelet count 5 . 109/l) is presented who developed an AMI (ST segment elevation myocardial infarction) and was successfully treated by primary percutaneous coronary intervention (PCI).Conclusion:Considering the high bleeding risk in patients with ITP and AMI, careful balance between usual anticoagulation and antiplatelet therapy on the one hand, and efforts to raise platelet count on the other hand are needed.ZusammenfassungHintergrund und Fragestellung:Akute Myokardinfarkte (AMI) bei Patienten mit idiopathischer thrombozytopenischer Purpura (ITP, Morbus Werlhof) sind seltene Ereignisse. Da in der Literatur nur einige wenige Fälle beschrieben sind, existieren auch keine Therapieempfehlungen für diese Konstellation. In der vorliegenden Studie sollen unterschiedliche Aspekte dieser herausfordernden Situation diskutiert und die verfügbaren Daten aus der Literatur zusammenfassend beschrieben werden.Fallbericht:Geschildert wird der Fall eines 80-jährigen Patienten mit ITP (Thrombozytenzahl 5 . 109/l), der einen AMI (ST-Strecken-Hebungsinfarkt) erlitten hatte und mit primärer perkutaner Koronarintervention (PCI) erfolgreich behandelt wurde.Schlussfolgerung:Das hohe Blutungsrisiko bei Patienten mit ITP und AMI erfordert eine sorgfältige Balance zwischen Antikoagulation bzw. Plättchenhemmung einerseits und Anhebung der Thrombozytenzahl andererseits.

Concomitant administration of simvastatin and danazol associated with fatal rhabdomyolysis.

BACKGROUND Simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, is indicated for the treatment of hypercholesterolemia and plays an important role in both the primary and secondary prevention of cardiovascular disease. Danazol is a steroid analogue approved for the treatment of endometriosis, fibrocystic breast disease, and hereditary angioedema. Despite not being licensed, danazol has been used for other off-label indications, such as idiopathic thrombocytopenic purpura (ITP), paroxysmal nocturnal hemoglobinuria, and aplastic anemia. OBJECTIVE We report a case of fatal rhabdomyolysis that occurred after concomitant administration of simvastatin and danazol in a patient with ITP. CASE SUMMARY An 80-year-old white male (height, 182 cm; weight, 90 kg) presented to the emergency department of the Clinical Hospital Centre Zemun, Belgrade, Serbia, with head injuries after an accidental fall caused by generalized weakness. He denied other complaints, except fatigue, mild pretibial edema, and progressive bilateral leg pain and cramping that began 7 days before. At the time of presentation, he was receiving aspirin 100 mg/d, clopidogrel 75 mg/d, ramipril 2.5 mg/d, pantoprazole 40 mg/d, danazol 600 mg/d, prednisone 60 mg/d, simvastatin 40 mg/d, and long-acting insulin 24 IU/d. After the injuries were treated, he was diagnosed with collapse and nasal contusion, and discharged without any changes in his therapy. Two days after initial presentation, the patient was readmitted to the hospital due to nausea, dark urine, and oliguria. All clinical signs (oliguria, dark urine, muscle pain, and tenderness) and laboratory markers (creatine kinase levels approximately 100 times the upper limit of normal, along with hyperkalemia, hyperphosphatemia, and hypoalbuminemia) were consistent with severe rhabdomyolysis. Despite intravenous hydration, forced diuresis, and hemodialysis, oliguria persisted and the patient died 6 days after admission. A score of 5 on the Naranjo adverse drug reaction probability scale was consistent with a probable association of rhabdomyolysis and concomitant treatment with simvastatin and danazol in this patient. CONCLUSIONS Statin-induced rhabdomyolysis must be considered whenever muscle or motor symptoms occur, especially when concomitant treatment with known inhibitors of statin metabolism is administered. Patients must be strictly monitored and the statin should be promptly discontinued with the onset of first signs and symptoms of myopathy. Clinicians should be aware of the potentially fatal consequences of both approved and unapproved treatments and be alert for the early detection of toxicity.

Visual assessment vs. strain imaging for the detection of critical stenosis of the left anterior descending coronary artery in patients without a history of myocardial infarction

AIMS We sought to determine the prevalence of overt and subclinical LV dysfunction in patients with critical left anterior descending coronary artery (LAD) stenosis but without a history of myocardial infarction and to compare diagnostic value of routine echocardiographic parameters with myocardial strain analysis for detection of critical LAD stenosis. METHODS AND RESULTS We retrospectively studied 269 patients with suspected coronary artery disease (CAD)-209 consecutive patients with critical LAD stenosis and 60 consecutive patients with atypical chest pain and without CAD. Conventional visual assessment of LV asynergy in the LAD territory was compared with global, regional, and segmental peak systolic longitudinal strain (PSLS) parameters derived by two-dimensional speckle tracking echocardiography (2D STE). Wall motion abnormalities in the LAD territory were found in 41% of patients with critical LAD stenosis, whereas, depending on the cut-off value, global longitudinal strain (GLS) was impaired in 42-69% of patients. GLS with an area under the receiver operating characteristic curve (AUC) of 0.85 showed better discriminative power for detecting critical LAD stenosis than conventional wall motion score index (AUC 0.73, P < 0.05, for the difference between the AUCs). PSLS values were significantly lower in basal and midventricular segments supplied by critically narrowed LAD, particularly if they also appeared dysfunctional on visual assessment. CONCLUSIONS Detection of subclinical LV dysfunction by 2D STE might improve identification of patients with critical LAD stenosis, although visually apparent regional LV dysfunction in the LAD territory is not uncommon finding in this subset of patients.

Myocardial mechanical and QTc dispersion for the detection of significant coronary artery disease

AIMS Ischaemic but viable myocardium may exhibit prolongation of contraction and QT interval duration, but it is largely unknown whether non-invasive assessment of regional heterogeneities of myocardial deformation and QT interval duration could identify patients with significant coronary artery disease (CAD). METHODS AND RESULTS We retrospectively studied 205 patients with suspected CAD who underwent coronary angiography. QTc dispersion was assessed from a 12-lead electrocardiogram (ECG) as the difference between the longest and shortest QTc intervals. Contraction duration was assessed as time from the ECG R-(Q-)wave to peak longitudinal strain in each of 18 left ventricular segments. Mechanical dispersion was defined as either the standard deviation of 18 time intervals (dispersionSD18) or as the difference between the longest and shortest time intervals (dispersiondelta). Longitudinal strain was measured by speckle tracking echocardiography. Mean contraction duration was longer in patients with significant CAD compared with control subjects (428 ± 51 vs. 410 ± 40 ms; P = 0.032), and it was correlated to QTc interval duration (r = 0.47; P < 0.001). In contrast to QTc interval duration and dispersion, both parameters of mechanical dispersion were independently associated with CAD (P < 0.001) and had incremental value over traditional risk factors, wall motion abnormalities, and global longitudinal strain (GLS) for the detection of significant CAD. CONCLUSION The QTc interval and myocardial contraction duration are related to the presence of significant CAD in patients without a history of previous myocardial infarction. Myocardial mechanical dispersion has an incremental value to GLS for identifying patients with significant CAD.

Prognostic significance of contractile reserve assessed by dobutamine-induced changes of Tei index in patients with idiopathic dilated cardiomyopathy

AIMS To determine prognostic significance of global left ventricular (LV) contractile reserve, defined by dobutamine-induced changes of Tei index (Delta Tei), in patients with dilated cardiomyopathy (DCM). METHODS AND RESULTS Thirty-eight patients with idiopathic DCM underwent high-dose (up to 40 microg/kg/min) dobutamine stress echocardiography. Prognostic value of different indices of LV contractile reserve, including Delta Tei, as well as changes of ejection fraction (Delta EF) and wall motion score index (Delta WMSi), was analysed. Patients were followed up for 5 years for cardiac mortality. Patients with preserved contractile reserve, defined by Delta Tei > -0.35, had significantly lower cardiac mortality when compared with those without it (38 vs. 77%, P = 0.02). Also, the Kaplan-Meier survival analysis revealed that patients with contractile reserve had better 5-year survival when compared with those without contractile reserve (log-rank = 6.01, P = 0.014). However, of all examined indices of contractile reserve, Coxs regression analysis identified Delta WMSi as the only independent predictor of 5-year mortality. CONCLUSION Our data indicate that the presence of contractile reserve assessed by Delta Tei may identify patients with favourable long-term prognosis. Prognostic value of Delta Tei appears to be similar to Delta EF, but less powerful than Delta WMSi.

Focus cardiac ultrasound core curriculum and core syllabus of the European Association of Cardiovascular Imaging

There is a growing trend of using ultrasound examination of the heart as a first-line diagnostic tool for initial patient evaluation in acute settings. Focus cardiac ultrasound (FoCUS) is a standardized but restricted cardiac ultrasound examination that may be undertaken by a range of medical professionals with diverse backgrounds. The intention of this core curriculum and syllabus is to define a unifying framework for educational and training processes/programmes that should result in competence in FoCUS for various medical professionals dealing with diagnostics and treatment of cardiovascular emergencies. The European Association of Cardiovascular Imaging prepared this document in close cooperation with representatives of the European Society of Anaesthesiology, the European Association of Cardiothoracic Anaesthesiology, the Acute Cardiovascular Care Association of the European Society of Cardiology and the World Interactive Network Focused On Critical Ultrasound. It aims to provide the key principles and represents a guide for teaching and training of FoCUS. We offer this document to the emergency and critical care community as a reference outline for teaching materials and courses related to FoCUS, for promoting teamwork and encouraging the development of the field.

Rational and design of EuroCRT: an international observational study on multi-modality imaging and cardiac resynchronization therapy

Aims Assessment of left ventricular (LV) volumes and ejection fraction (LVEF) with cardiac imaging is important in the selection of patients for cardiac resynchronization therapy (CRT). Several observational studies have explored the role of imaging-derived LV dyssynchrony parameters to predict the response to CRT, but have yielded inconsistent results, precluding the inclusion of imaging-derived LV dyssynchrony parameters in current guidelines for selection of patients for CRT. Methods The EuroCRT is a large European multicentre prospective observational study led by the European Association of Cardiovascular Imaging. We aim to explore if combing the value of cardiac magnetic resonance (CMR) and echocardiography could be beneficial for selecting heart failure patients for CRT in terms of improvement in long-term survival, clinical symptoms, LV function, and volumes. Speckle tracking echocardiography will be used to assess LV dyssynchrony and wasted cardiac work whereas myocardial scar will be assessed with late gadolinium contrast enhanced CMR. All data will be measured in core laboratories. The study will be conducted in European centres with known expertise in both CRT and multimodality cardiac imaging.